From Oxygen to X-Rays: Different Nanotechnology Approaches for Cancer Treatment

• Grant number: 24/21657-2
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2028
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Éder José Guidelli
• Grantee: Éder José Guidelli
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Hybrid core-shell nanoparticles (NPs) have potential applications in X-ray activated photodynamic therapy (X-PDT), where the drug is activated by X-rays due to the NP scintillation, combining radiotherapy (RT) and PDT into a single treatment. X-PDT offers the potential to reduce the dose of X-rays required to cause tumor cell death in RT, minimizing damage to healthy tissues surrounding the tumor and reducing late radiation effects. From the PDT perspective, the use of X-rays enables the treatment of deep-seated tumors located in areas inaccessible to visible light. Another approach to combine RT and PDT is using NPs capable of carrying singlet oxygen (¹O¿) and releasing it upon stimulation with X-rays. This strategy can enhance RT efficacy through both the direct action of ¹O¿ and the reduction of hypoxia. Considering that reducing hypoxia increases radiosensitization, another approach to boosting RT efficacy involves using scintillating NPs functionalized with drugs capable of photo-releasing nitric oxide (NO). This radical can enhance blood flow and, consequently, oxygen delivery to the tumor. This project will explore three types of nanoparticles: 1) Hybrid NPs consisting of a lanthanide scintillating core coated with a photosensitizer to produce singlet oxygen during X-ray exposure; 2) Scintillating NPs functionalized with drugs that photo-release nitric oxide upon X-ray exposure; 3) Hybrid NPs with a metallic core coated with molecules capable of trapping singlet oxygen ex situ and releasing it inside cancer cells upon X-ray activation. The project involves synthesizing and characterizing the nanoparticles, functionalizing them, and performing tests to verify the production or release of reactive species. Clonogenic assays will be conducted to evaluate whether the nanoparticles can reduce the reproductive capacity of cancer cells when irradiated with ionizing radiation. (AU)